Hepatitis C virus (HCV RNA virus) is the cause of hepatitis C. Infection occurs from body fluids such as the blood.
Hepatitis C virus (HCV) is classified into several subtypes according to the genetic type. There is a classification system which classifies HCV into types 1-6 and subtypes a, b, and c, which can be written as 1a, 1b, 2a, 2b, 3a, 3b, and so on (for example, Kato N., Hepatitis C Virus, Industrial Publishing & Consulting, Inc., Tokyo, 2000, p 168).
Sixty percents of people infected with HCV develop acute hepatitis after going through a 1-2 month incubation period. However, those infected with hepatitis C exhibit hepatic damage and slight symptoms, wherein the acute hepatitis period is not very clear. Acute hepatitis C advances to chronic hepatitis at a high rate (60-70%). Chronic hepatitis C causes abnormal AST (aspartate aminotransferase (also known as GOT, glutamate oxaloacetate transaminase)) and ALT (alanine aminotransferase (also known as GPT, glutamate pyruvate transaminase)) values. However, after 2-3 years, these values return to normal or close thereto. Since this state continues from several years to 10 years, doctors sometimes diagnose patients with chronic hepatitis C more than 10 years after the patient was infected with HCV After repeated chronic necrotic and inflammatory reactions of the liver cells over a period of 20-30 years, hepatitis is known to progress into cirrhosis, and after a further 10 years, the cirrhosis progresses into liver cancer (Kumagai Naoki., Hepatitis C, Mainichi Life, September 2002 issue, p 23, The Yomiuri Shimbun, 2002).
In chronic hepatitis C patients, subjective symptoms are only recognizable during the active period. Symptoms include general malaise, malaise, poor appetite, nausea, and vomiting. If the disease continues to progress into cirrhosis, the percentage of patients exhibiting subjective symptoms rises to 80%. These patients exhibit additional symptoms such as a bloating sensation and skin pruritus. These patients may also exhibit symptoms such as abdominal pain, hematemesis, and melena. Major objective symptom is hepatic enlargement, and the incidence is estimated to be 60 percents. Other objective symptoms include enlargement of the left hepatic lobe, splenomegaly, swelling, ascites, erythema palmare, jaundice, and the like (Kato N., Hepatitis C Virus, Industrial Publishing & Consulting, Inc., Tokyo, 2000, p 189).
As a general therapeutic strategy for treating hepatitis C, the function of the liver is normalized and hepatitis is calmed for suppression of a disease progression. Based on the idea that the disease progression is suppressed by the calming of hepatitis while the virus exists in the body, a treatment comprising administering ursodeoxycholic acid (component comprising fel ursi), minor Bupleurum (Chinese herbal medicine comprising a decoction of seven crude drugs including Bupleurum root, scutellaria, pinellia tuber, (dried) fresh ginger, ginseng, jujube, and licorice), or a preparation comprising glycyrrhizinate of licorice as major constituents (strong neominophagen-C (SNMC®), in order to improve or reduce symptoms is widely known.
However, a more vigorously pursued method known as interferon (IFN) treatment for HCV viral clearance in the body in order to stop progress of the disease. In IFN treatment, two types of IFNs (α and β) are used for antiviral agents such as nIFNα (natural interferon α), recombinant IFNα (genetic recombination-type interferon α), nIFNβ (natural interferon β), and consensus IFNα [consensus interferon α: interferon alphacon-1 (genetic recombination)]. There have been reported the complete responder from whom the virus is completely removed and the incomplete responder who is remarkably improving the hepatic functions by the use of IFN. IFN has also been acknowledged with the effect of suppression of the progress by decreasing the rate of the production of liver cancer.
In addition to IFN, lactoferrin can be given as a substance possessing an anti-virus effect on HCV. Lactoferrin is a glycoprotein belonging to the iron-binding trans-family having a molecular weight of about 80,000 and is obtained by binding a sugar chain of galactose or mannose to a polypeptide chain. The action mechanism of lactoferrin is believed to be the neutralization of the extracellular virus, thereby preventing infection.
It has been disclosed that when one or more of Cucurbita moschata, Plantago asiatica, and Lonicera japonica are added to feed, diseases, especially natural infections, caused by parasites, bacteria, and viruses are largely prevented, an enhancement of the biophylaxis, and an improvement of the quality of meets or eggs. Furthermore, it has been disclosed that a feed comprising crude drugs of Cucurbita moschata, Plantago asiatica, Lonicera japonica, and Carthamus tinctorius improves the health conditions, survival rates, quality of egg, and has anti-leucocytozoonosis effect in layers, and has an anti-Newcastle disease effect and inhibitory effects of the decreased number of Coccidium and Staphylococci in the intestine of quails (U.S. Pat. No. 5,882,672).
A method for producing an interferon inducer from the plants of the genus Cucurbitaceae such as pumpkin has been disclosed (U.S. Pat. No. 4,421,746). It has been disclosed that a methanol extract of winter squash (Sudan medicinal plant) exhibits an HCV protease inhibitory effect and that the inhibitory activity is 47.4±0.0% (Phytochemistry Research (2000) 14, 510-516). However, in this document, there is neither disclosed nor suggested about the decrease in hepatitis C virus under in vivo study. Also, it has been disclosed that Plantago asiatica (Plantago major L.) is used in the treatment of hepatitis virus (American Journal of Chinese Medicine, (1990) Vol. XVIII, Nos. 1-2, pp 35-43). However, this document reported that the treatment can be used for hepatitis which did not know exactly as hepatitis C, but did not mention or indicate that the treatment is actually effective. The antiviral activity and anti-tumor activity of interferon inducers extracted from the flowers of Carthamus tinctorius has been disclosed (for example, U.S. Pat. No. 4,456,597). It has also been disclosed that interferon inducers may be extracted from the flowers of Lonicera japonica, seeds of Plantago asiatica, and the like, and that the extracted interferon inducers are useful for the preventive and curative treatments of viral infections in humans and animals (U.S. Pat. No. 4,469,685). A macrophage activator comprising two crude drugs of Cucurbita moschata and Carthamus tinctorius has also been disclosed (JP-A-11-116498). A neutrophil activator comprising four crude drugs of Cucurbita moschata, Carthamus tinctorius, Plantago asiatica, and Lonicera japonica has also been disclosed (JP-A-2000-281584). However, while these documents disclose the interferon inducing effects, macrophage activating effects, neutrophil activating effects, and the inhibitory action of IgE anti-body production of the crude drugs used as active components in the present invention, none of the references disclose or suggest the hepatitis C antivirus activity of these crude drugs.
The progress of a curing method for “refractory chronic hepatitis C” which corresponds to the case that the patient carries a large amount of the virus in the blood (generally 100 KIU/ml or more) in particular among the chronic hepatitis C, type 1b has been desired (Kumagai Naoki, Hepatitis C, Mainichi Life, September issue, The Yomiuri Shimbun, Tokyo, 2002). Even when using interferon alphacon-1, which has been introduced into the market as a hepatitis C curing agent with the highest complete recovery rate, it is reported that a complete recovery can not be expected if the amount of the virus is not less than 850 KIU/ml. It is known that the lower the amount of the virus, the better the recovery effect of the interferon treatment (1995 report of the Anti-hepatitis A and B Study Group of the Ministry of Health and Welfare, Progress of Medicinal Science, separate volume, “Search for the Onset and Progress Mechanism of Liver Disorders”, issued on Feb. 5, 1999, Ishiyaku Publishers, Inc. Kan Tan Sui 43, (2), pp 281-288, 2001). Therefore, it is desirable for the amount of the virus to be as low as possible before starting the interferon treatment.